ManagingPain:

KeyPointsSpecialPainManagementCommission19September2016

DanielB.Carr,M.D.

ProfessorandDirector,PainResearch,EducationPolicy(“PREP”)Program

TuftsUniversitySchoolofMedicine

Today’sTalk

Updateonpainpharmacotherapyandtheoptimalsequencefornondruganddrugtreatments(includingopioids)

Citetools,instrumentstoincreasecomfortlevelandefficiency,raisesatisfactionscores,decreaserisk

Presentevidenceforchronicpainasahighlyprevalentdiseaseentityperse

Whentorefertoapainspecialist

ChronicPainTherapy:Goals

Decreasepainintensity(restingandwithactivity):NOTEonlyonedimension

ImproveotherdimensionsofHRQOL

Rehabilitate/restore(PT,OT,psychology)

Vocationalcounseling/retraining,re-entry

“Bigpain,smalllife”to“smallpain,biglife”

Curesometimes,treatoften,carealways

SLOTMACHINE

PERSONPAINPRODUCT

PAINHISTORY:DRILLINGDOWN

Onset

Site(diagram)

Character(NPP)

Intensity(resting,movement,now,worst)

Effects(sleep,work,function,family,mood)

Meaning(expectations,beliefs,knowledge,culture)

CAMuse(acupuncture,hypnosis,etc)

INITIAL+F/UEVALUATIONS

Documenttherapies,PGE,targetedphysicalexam

Substanceabuserisk(e.g.,alcohol)

–ForopioidRxconsiderSOAPPinitially,thenCOMM

Trackoutcomes

–Physicalfunction(MPI,BPIinterferencescale)

–Emotionalfunctioning(Beckdepression,POMS)

–Overallimprovement(PGEchange)

–Painintensity(0-10VRSBUTfunctionoftenbetterindex)

Labtesting--UDT

Assessneedtoadjusttreatmentplanorrefer

PAIN101:BASICMENU

Non-drugmethods(inclIntegrative,CAM)

–Physicalmeasures(heat,cold,splint)

–Cognitive-behavioral(cf.PTSD)

–ProvenefficacybymultipleRCTs,M-As

Drug

–NSAIDs(notallalike;ceilingforbenefit,notrisk;Solomonetal,ArchIntMed2010)

–Opioids(varieddrugs,dosageforms,people)

–Localanesthetics(topicalorinjected)

–Adjuvants(boosteffects,Rxside-effects)

NSAIDs:OVERVIEW

Original,mostwidelyusedsyntheticanalgesics

Classifiedbychemicalstructure

First-linepaintherapyinacute,chronicandcancer-relatedpain

Componentofmultimodalanalgesia

Considerablemorbidity,mortalityworldwide(GI,renal,CV,platelet)2015FDAalert

TraditionalNSAIDshavelimitedselectivelyforCOXisoforms;COX-2selectiveagents=“coxibs”

Low-doseASAusefulforMI,stroke,colonCaprophylaxis

COXIBS:CVRISKS

Mukherjee(2001)comparedannualizedratesofMIfromCLASSandVIGORwithpooled placebogroup(N=23,000)resultsfrom4ASApreventiontrials.

AnnualizedMIrates0.52%fromplacebogroup,0.80%forCelecoxib(P0.02),0.74%forRofecoxib(P=0.04)

2005FDA,MHRAmemoscautionedagainstlong-(orforparecoxib,short-)termuseofNSAIDsduetoCVrisks;rofecoxibandvaldecoxibwithdrawn,parecoxibnon-approved

Celecoxibremains(n.b.meloxicam,diclofenac)

ContinuumofRisk:COX-1vsCOX-2

CVRiskStroke

ClotMIBP

EDGE

VIGOR

CLASS

GIRisk

UlcerGIbleed

COX-2COX-1

1111

PARACELSUS(1493-1541)

Allsubstancesarepoisons;thereisnonewhichisnotapoison.Therightdosedifferentiatesapoisonfromaremedy.

ADJUVANTMEDICATION

Adrugusedtoenhanceeffectivenessofa10analgesic–typicallyanopioid--orreducesideeffect(s)ofa10analgesic

AlthoughNSAIDs,COXIBSandLAsfitthisdefinition,byconventiontheyaregenerallyexcluded

Inpractice,referstoAEDs,TCAs,etcespeciallywhenappliedtotreatneuropathicpain

Antidepressants

–TCA(e.g.,amitriptyline,imipramine…)SSRI(e.g.,fluoxetine),SNRI(e.g.,duloxetine)

–30%ofpatientswithneuropathicpaingivenantidepressantswillobtain50%painrelief

–30%willhaveminorAEs

–4%willceasetreatmentduetomajorAEs

–Limitedliterature,butnocleardifferenceinefficacyacrossconditionsordrugs

Anticonvulsants

–gabapentin,pregabalin,clonazepam,

–valproate,lamotrigine,topiramide,zonisamide,oxcarbazepine,levotireacetam,[carbamazepine(TGN),phenytoin]

–NNT=1.6foreffectiveness,2.4forAEs,39.3fordrug-relateddropoutinRCTs(exc.gabapentin)

–Demant(Pain,2014):phenotypingirritablevs

nonirritablenociceptortoguideRx?

AEDsBetterfor“Irritable

Nociceptor”PeripheralNPP?

Demantetal,Pain2014:Oxcarbazepine[Trileptal]

ADJUVANTS(3)

Na+(mexiletine)orCa++blockers

NMDAantagonists(ketamine,dextromethorphan,amantadine…N.B.alsodextropropoxyphene,methadone)

Alpha-2agonists(clonidine,tizanidine)

GABAagonist(baclofen)

Phenothiazines,thioxanthines

Butyrophenones(haloperidol)

+Topicalagents(lidocaine,capsaicin)

MARCUSAURELIUS(121-180)

Whenunbearable,paindestroysus…Recollectthis,too,thatmanyofoureverydaydiscomfortsarereallypainindisguise,such asdrowsinessorwantofappetite.

Meditations(c.160)

INDIVIDUALVARIABILITY

Genetic:preclinical,clinical

Gender

Priorsensitization(oftenpresentonHx)

Psychosocial(litigation/compensation,job/familysatisfaction,spousalsolicitousness,premorbiddepression,abuse)

Clinician-patientinteraction(?enabling,medicalizingasomatoformdisorder) 19

OpioidGuidelines:SharedElements(CDC 2013)

PEx,painHx,pastmedicalHx,family/socialHx

Urinedrugtesting,whenappropriate

Consideralltreatmentoptions,weighingbenefitsandrisksofopioidtherapy,andusingopioidswhenalternativetreatmentsareineffective

Startpatientsonlowesteffectivedose

Paintreatmentagreements

Document/monitorongoingpain,Rxprogress,PDMP

Usegreatervigilanceathighdoses

Usingsafeandeffectivemethodsfordiscontinuingopioids(e.g.,tapering,specialistreferra20ls)

“QualityOpioidPrescribing”

(BCBSofMA,2012)

Treatmentplanincludingacleardiagnosis,explciitgoals,andexplorationofothertreatmentoptions

Informedconsentandformalassessmentofaddictionrisk(excludescancer,end-of-life)

WrittenagreementbetweenprescriberandpatientaddressingissuesofRxmanagement,diversionanduseofothersubstances

AccountableRxgroup,useof1pharmacy/chain

Urinedrugtesting+specifics(e.g.,2x15dayRx)

5StepsofOpioidPrescribing

AssesspainAbuserisk(RxAgreement)

BelieveButverify(UDT)

ChooseperContext

DeliverRxDeliberatelyandcarefully(PMP)

Enable,Empower:focusonfunction

AdaptedfromJacox,Carr,Payneetal,1994

Pain:aPublicHealthIssue

IOM,WHOhavedeclaredpainapublichealthissue:

•Highprevalence,burden

•Amenabletoprevention(e.g.,acute-to-chronictransition)

•Population-basedphenomenonwithclearrelationtoSES

•Humanrightsdimensionincludinginequitiesin

access23

DyadicvsSupradyadic

HealthcareModels

SmithandChristakis,AnnRevSociology(2008)

24

PainvsRejection(Wager2013)

“Comparisonsofrejecterversusfriendandpainversuswarmthyieldedsimilarlevelsofself-reportednegativeaffect,andoverlappingportionsofmanyregionsrelatedtopainintensitywereactivated(bilateralanteriorinsula,medialthalamus,secondarysomatosensorycortex,anddorsalposteriorinsula)2.”5

ThePerfectAnalgesic?

PAIN202:PAINASADISEASE

(SiddallandCousins,2004)

Injurytriggersacascadeofresponses

PNS,CNSpromptlyadapt,reorganize,remember

“Programmedinstability”linkspain,memory

Acuteandchronicpain=continuum

Increasingdocumentationofchronicneuropathicpainaftersurgery(NNH2-7)

UnclearwhyNNHisn’t=1

SPECIALISTREFERRAL?

“Buildanetworkofclinicalexpertstowhomyoucanturn”[Fishman]

“Knowyourlimitsandreferearly”

“Bespecificinyourrequestsandinturnexpectcommunicationback”

Why?clarifydiagnosis;specializedorinvasiveRx;titratingmultimodalregimen(~DM);failuretoimproveHRQOL(notPI)

Nondrug/non-opioidRxwheneverpossible

Validate,titratechronicopioidRx